case report treating methamphetamine-induced resistant...

Case ReportTreating Methamphetamine-Induced ResistantPsychosis with Clozapine

Ruohollah Seddigh, Amir-Abbas Keshavarz-Akhlaghi, and Behnam Shariati

Mental Health Research Center, Faculty of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry,Iran University of Medical Sciences, Tehran, Iran

Correspondence should be addressed to Amir-Abbas Keshavarz-Akhlaghi; [email protected]

Received 14 July 2014; Revised 9 October 2014; Accepted 10 October 2014; Published 28 October 2014

Academic Editor: Shusuke Numata

Copyright © 2014 Ruohollah Seddigh et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment,lacking any obvious treatment methods for its resistant cases. Aims of Case Report. In the present study, a number of two cases oftreatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both casescompletely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up. Conclusion.Because of its particular pharmacologic features, clozapine may be effective in treating MIP.

1. Introduction

During recent years, methamphetamine abuse has increasedand turned into a serious concern [1–3]. Studies have shownthat a chronic use of methamphetamine is accompanied byneurotoxicity, cognitive and psychiatric dysfunctions, andseveral performance-related troubles [4, 5] imposing hugecosts on individuals, families, and society as well [6]. How-ever, what has caused its abuse turning into a serious concernis psychosis induced by it, with it changing into a challenge forthe health and treatment system in Iran [7]. Solely, a singleexperience of substance abuse among the individuals withan underlying psychotic disorder precipitate psychosis in 50–70% of such cases [8]; and among those individuals withoutany underlying factors, it may cause different types of short-term, long-term, and periodic psychosis or even those typesbeing resistant to treatment with antipsychotic medications[5, 9, 10].

From treatment perspective, although some typical andatypical antipsychotics have been utilized in treating MIP[11], few studies have been conducted regarding resistantpsychotic cases. For instance, some reports on the efficacyof electroconvulsive therapy (ECT) among these patients[12]. Moreover, this group of patients seems to have muchheterogeneity in their responding to treatment [9].

Thepresent report involves a treatment description of twopatients affected by MIP, the symptoms of whom were onlycured by taking clozapine. Our searches revealed that no useof clozapine has been reported in treating MIP yet.

2. Case Presentation

The First Patient. The first patient is a 34-year-old man,single, having primary education, a house painter. He beganto consume opium, then heroin at the age of 20, andmethamphetamine at the age of 25. During last 9 years, hewas hospitalized 12 times due to MIP at psychiatry hospitals.In each hospitalization time, the symptoms were removedby different antipsychotic drugs in only 1-2 weeks; and theirrelapse again happened due to avoiding taking drugs andstarting to consume it as well. In last 6 months, however,despite methamphetamine withdrawal, psychosis continuedto remain. In psychiatric examinations, paranoid delusionand commanding auditory hallucinations were reported.Besides, the patient also complained about anxiety and occa-sional insomnia. He was totally alert answering our questionsquite well. However, he was unaware of his psychotic states.In last 6 months, in spite of treatment with the followingmedications (each prescribed for 4 weeks), the symptoms

Hindawi Publishing CorporationCase Reports in PsychiatryVolume 2014, Article ID 845145, 4 pageshttp://dx.doi.org/10.1155/2014/845145

2 Case Reports in Psychiatry

were not removed: olanzapine: 15mg daily; risperidone: 6mgdaily; and thiothixene: 15mg daily.

Due to a failure in recovery from disease, the patientreceived 6 sessions of ECT. Each session caused seizurelasting averagely for 45 seconds (35–60 seconds) which wasobserved in the form of muscle contraction in patient’sbedside. Due to an occurrence of a long seizure (lastingfor 130 seconds) in the 6th session and avoiding it throughdiazepam intravenous injection, ECT sessions were termi-nated. During these therapeutic sessions, no change wasobserved in patient’s psychotic state. Eventually, a treatmentplan with clozapine (25mg daily) was started and graduallytitrated to 150mg daily. As a result, psychosis was completelyremoved in only 2 weeks. In an 8-month follow-up andregarding clozapine consumption to be continued, no relapsein psychotic symptoms was observed. Concerning drugabuse, the patient was in “early full remission” based onDSM-IV-TR criteria despite the fact that he was not in acontrolled environment. Thus, he completely withdrew fromany substance abuse and returned to his work.

The patient’s familial background, regarding axis-I psy-chiatric disorders, was negative. Moreover, the patient him-self had no background of axis-I psychiatric disorders priorto methamphetamine abuse. However, considering the exis-tence of oppositional behaviors in his childhood and adoles-cence as well as his interview and results of questionnaire ofStructured Clinical Interview for DSM-IV-TR Axis II (SCID-II), a diagnosis of antisocial personality disorder was evidentfor him.According tomedical examinations, Complete BloodCount, tests of thyroid, liver and kidney functions, and testson different hepatitis types and human immunodeficiencyvirus (HIV) as well as brain MRI were all normal. Besides,after the 6th session of ECT in neurologic counseling, nopathologic point was seen.Thus, it was merely advised to thatECT be terminated.

The Second Patient. The second patient is a 29-year-old man,single, having secondary education. He started substanceabuse since he was 15 and has consumed all kinds of illegaldrugs in Iran. However, he was affected by psychosis for thefirst time due to methamphetamine abuse since 6 monthsago. In last 3 months, however, despite methamphetaminewithdrawal, psychosis continued to remain. In the patient’sfirst visit to psychiatry clinic, persecutory delusion, referencedelusion, somatic hallucinations (in a way that the patientfelt an outer thing under his hand skin), and olfactoryhallucinations (in a way that he felt the smell of opium) aswell as anxiety, irritation, and loss of libido were seen. Due tobeing aggressive, the patient was hospitalized in psychiatricemergency department. Then, clonazepam (6mg daily) wasprescribed for him. In 24 hours, he was seen to be muchcalmer. However, he was unaware of his psychotic states.In last 6 months, despite treatment with the medicationsmentioned below (each lasting for 3 weeks), in spite of con-trolling aggression, psychosis was not removed: olanzapine:15mg daily; risperidone: 5mg daily; quetiapine 600mg daily;and haloperidol: 10mg daily. Eventually, all drugs prescribedpreviously were avoided and clozapine (with a dosage of100mg daily), together with clonazepam (2mg daily), started

to be prescribed. One week after clozapine prescription,clonazepam was discontinued. In a 9-month follow-up andwith the continuance of clozapine consumption, no signs ofpsychosis relapse were seen. Concerning drug abuse, he hadno other abuse experience; and the patient returned to hiswork. So, he was in “early full remission” based on DSM-IV-TR criteria despite the fact that he was not in a controlledenvironment.

The patient’s familial and personal backgrounds, regard-ing axis-I psychiatric disorders were negative. However, adiagnosis of antisocial personality disorder was evident forhim.Moreover, similar to the previous patient, all paraclinicalexaminations proved to be negative.

3. Discussion

Although MIP alleviates after a short period of time amongnumerous patients, it may last for several months in spiteof stopping its abuse and taking antipsychotics as well; thus,pharmacologic therapy is indicated [9]. In many of studies,atypical antipsychotics have been prescribed in order to treatMIP, and the efficacy of such drugs as risperidone [13],olanzapine [14], quetiapine [15, 16], and aripiprazole [17] intreating it to some extent has been demonstrated. However,in the state of drug-resistant psychosis, there is no reliableevidence. For example one study has reported the positiveinfluence of ECT in these cases [12]. In the present study,clozapine was prescribed due to the patients’ not respondingto these treatmentmethods. Both patients continued to sufferfrom psychosis even after receiving at least 3 periods oftreatment with nonclozapine antipsychotics. However, theirsymptoms were completely removed in only a short timeperiod since taking clozapine.

From a neuroanatomical perspective, methamphetamineabuse with a low dosage causes damage to serotonergicpathways in areas of frontal cortex and hippocampus; andits high dosage abuse leads to some damage to striatumand parietal cortex [4, 18]. Considering neurotransmitters,methamphetamine leads to the release of high amountsof dopamine, norepinephrine, and serotonin in the brain,especially in striatum and its related areas [19]. But, in the caseof its long-term abuse, it decreases not only the density of theabove-mentioned neurotransmitters (especially dopamine)in the brain due to its neurotoxic effects [18] but also thenumber of D

2dopamine and dopamine transporter receptors

[20]. Such effects may continue to occur even after a longwithdrawal from abuse. On the other hand, a long-term abuseofmethamphetaminemay cause noradrenergic hyperactivity,individuals’ sensitivity to stress, and psychosis relapse [21].Moreover, studies have shown that, in patients affected bya spontaneous relapse of psychosis after a long-term with-drawal, when they experience flashbacks, the norepinephrineand 3-methoxytyramine (the major metabolite of dopamine)blood levels are high in their blood [22]. The above profilerepresents the major excitatory effects of methamphetamine.

On the other hand, among antipsychotics, clozapinepossesses unique features, compared to other antipsychotics.Clozapine has a high affinity towards 5-HT

2receptor block-

ade. This receptor has huge stimulating effects in the brain

Case Reports in Psychiatry 3

and is blocked to a high extent as the patient takes clozapine.Moreover, clozapine is a strong blocker of 5-HT

3as well as

𝛼1and 𝛼

2adrenergic receptors [23]. Regarding this profile,

clozapine seems to overcome adrenergic and serotonergicarousal seen in methamphetamine abuse. Thus, it may beconsidered as a treatment for MIP. Among other antipsy-chotics, such effects are also observed in aripiprazole [24];however, according to very limited studies available, this drugjust reduces the severity of psychosis in MIP [17]. Due to itsunavailability, aripiprazole was not prescribed for the patientsin this study.

Among clozapine effects, one other unique effect is itslower infinity towards D

2receptor blocks, compared to other

antipsychotics in general, and toward many of D2receptor

blocks in mesolimbic areas, compared to those receptorsin striatum areas [23]. This means that, considering neu-ropathology, mesolimbic areas may receive more importancethan striatum areas do among those patients affected by MIP,with this demanding more future research on it.

The other important point made about the two patientsin this report is their being in early full remission in an 8-9 follow-up. This means that clozapine may expert positiveeffect on some aspects related to methamphetamine abusesuch as craving, those mood symptoms accompanied bypsychosis, anxiety, and aggression. However, more controlledresearch needs to be done in an attempt to confirm this.

Abbreviations

MIP: Methamphetamine-induced psychosisECT: Electroconvulsive therapy.

Consent

Written informed consent was obtained from the patients forpublication of this report. A copy of the consent is availablefor review.

Conflict of Interests

The authors declare that they have no competing interests.

Authors’ Contribution

Ruohollah Seddigh and Amir-Abbas Keshavarz-Akhlaghireported two cases and wrote them. Behnam Shariatidesigned the report and edited the paper. All authors read andapproved the final paper.

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4 Case Reports in Psychiatry

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